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Molecular and Cellular Biochemistry

, Volume 383, Issue 1–2, pp 39–48 | Cite as

Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins

  • Sojung Park
  • Dong Hyung Cho
  • Ladislav Andera
  • Nayoung Suh
  • Inki KimEmail author
Article

Abstract

The TNF-related apoptosis inducing ligand (TRAIL) has promising anti-cancer therapeutic activity, although significant percentage of primary tumors resistant to TRAIL-induced apoptosis remains an obstacle to the extensive use of TRAIL-based mono-therapies. Natural compound curcumin could potentially sensitize resistant cancer cells to TRAIL. We found that the combination of TRAIL with curcumin can synergistically induces apoptosis in three TRAIL-resistant breast cancer cell lines. The mechanism behind this synergistic cell death was investigated by examining an effect of curcumin on the expression and activation of TRAIL-associated cell death proteins. Immunoblotting, RNA interference, and use of chemical inhibitors of TRAIL-activate signaling revealed differential effects of curcumin on the expression of Mcl-1 and activities of ERK and Akt. Curcumin-induced production of reactive oxygen species did not affect total expression of DR5 but it enhanced mobilization of DR5 to the plasma membrane. In these breast cancer cells curcumin also induced downregulation of IAP proteins. Taken together, our data suggest that a combination of TRAIL and curcumin is a potentially promising treatment for breast cancer, although the specific mechanisms involved in this sensitization could differ even among breast cancer cells of different origins.

Keywords

TRAIL Curcumin Apoptosis Breast cancer 

Notes

Acknowledgments

This research was supported by the Yujeonja-Donguibogam project based on Traditional herbs (Grant No. 2012M3A9C4048793), Republic of Korea, and by the International Research & Development Program of the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (MEST) of Korea (Grant No. NRF-2012K1A3A1A07045330), and by the Grant (2012-512) from the ASAN Institute for Life Sciences, Seoul, Korea.

Conflict of interest

The authors have no conflicts of interest to declare.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sojung Park
    • 1
  • Dong Hyung Cho
    • 3
  • Ladislav Andera
    • 4
  • Nayoung Suh
    • 1
    • 2
  • Inki Kim
    • 1
    • 2
    Email author
  1. 1.Asan Institute for Life SciencesAsan Medical CenterSeoulRepublic of Korea
  2. 2.Department of MedicineUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  3. 3.Graduate School of East-West Medical ScienceKyung Hee UniversityYonginRepublic of Korea
  4. 4.Institute of Molecular GeneticsAcademy of Sciences of the Czech RepublicPrague 4Czech Republic

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